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AO-176 in Multiple Solid Tumor Malignancies

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ClinicalTrials.gov Identifier: NCT03834948
Recruitment Status : Recruiting
First Posted : February 8, 2019
Last Update Posted : April 15, 2022
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Arch Oncology

Tracking Information
First Submitted Date  ICMJE February 4, 2019
First Posted Date  ICMJE February 8, 2019
Last Update Posted Date April 15, 2022
Actual Study Start Date  ICMJE February 4, 2019
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 3, 2021)
  • Safety of AO-176 assessed by adverse events and laboratory abnormalities [ Time Frame: Up to 12 months ]
    Evaluate the safety of AO-176 measured by the number adverse events, serious adverse events and lab abnormalities.
  • Safety of AO-176 and paclitaxel assessed by adverse events and laboratory abnormalities [ Time Frame: Up to 12 months ]
    Evaluate the safety of AO-176 in combination with paclitaxel measured by the number adverse events, serious adverse events and lab abnormalities.
  • Safety of AO-176 and pembrolizumab assessed by adverse events and laboratory abnormalities [ Time Frame: Up to 12 months ]
    Evaluate the safety of AO-176 in combination with pembrolizumab measured by the number adverse events, serious adverse events and lab abnormalities.
Original Primary Outcome Measures  ICMJE
 (submitted: February 6, 2019)
Safety Of AO-176 assessed by adverse events and laboratory abnormalities [ Time Frame: Up to 12 months ]
Evaluate the safety of AO-176 measured by the number adverse events, serious adverse events and lab abnormalities.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2021)
  • AO-176 anti-tumor activity assessed by changes in response criteria [ Time Frame: Up to 12 months ]
    Evaluate objective response rate of AO-176 using RECIST v1.1 and iRECIST.
  • AO-176 + paclitaxel anti-tumor activity assessed by changes in response criteria [ Time Frame: Up to 12 months ]
    Evaluate objective response rate of AO-176 in combination with paclitaxel using RECIST v1.1 and iRECIST.
  • AO-176 + pembrolizumab anti-tumor activity assessed by changes in response criteria [ Time Frame: Up to 12 months ]
    Evaluate objective response rate of AO-176 in combination with pembrolizumab using RECIST v1.1 and iRECIST.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2019)
AO-176 Anti-Tumor Activity assessed by changes in response criteria [ Time Frame: Up to 12 months ]
Evaluate Objective response rate of AO-176 using RECIST and iRECIST.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE AO-176 in Multiple Solid Tumor Malignancies
Official Title  ICMJE A Phase 1/2 Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of AO-176
Brief Summary This is a first-in-human, Phase 1/2 multi-center, open-label, dose escalation and expansion study of AO-176 which will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and clinical effects of AO-176 in patients with advanced solid tumors.
Detailed Description

This is a first-in-human, Phase 1/2 multicenter, open-label, dose escalation and expansion study of AO-176 in patients with solid tumors. Part A of this study will examine escalating repeat doses of AO-176 monotherapy in patients with select advanced solid tumors, including epithelial ovarian carcinoma (EOC), which will include primary peritoneal and fallopian tube carcinoma; squamous cell carcinoma of the head and neck; endometrial carcinoma; castration resistant prostate cancer; non-small cell lung adenocarcinoma; papillary thyroid carcinoma; pleural or peritoneal malignant mesothelioma; and gastroesophageal adenocarcinoma, for which standard therapy proven to provide clinical benefit does not exist or is no longer effective.

Part B and Part C of this study will examine escalating repeat doses of AO-176 in combination with paclitaxel (Part B) or pembrolizumab (Part C) in platinum-resistant EOC, including primary peritoneal and fallopian tube carcinoma; endometrial carcinoma; and gastric adenocarcinoma/gastroesophageal adenocarcinoma.

The monotherapy and combination dose escalation portions of the study utilize a classic 3+3 design, with enrollment of 3 patients per cohort and expansion of the cohort in the event of a dose-limiting toxicity (DLT).

Once the maximum-tolerated dose (MTD)/recommended phase 2 dose (RP2D) has been established in dose escalation, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy of AO-176 as monotherapy, in combination with paclitaxel, and in combination with pembrolizumab.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Each dose escalation cohort will initially recruit 3 patients to receive AO-176 or AO-176 + paclitaxel or AO-176 + pembrolizumab in a standard 3+3 design; the cohort will be expanded in the event of a DLT.

Once the MTD/RP2D has been established for monotherapy, AO-176 + paclitaxel or AO-176 + pembrolizumab, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE
  • Drug: AO-176
    Humanized monoclonal antibody (mAb) targeting CD47
  • Drug: AO-176 + Paclitaxel
    Humanized monoclonal antibody (mAb) targeting CD47 and paclitaxel
  • Drug: AO-176 + Pembrolizumab
    Humanized monoclonal antibody (mAb) targeting CD47 and pembrolizumab
Study Arms  ICMJE
  • Experimental: AO-176 Dose Escalation
    Each dose escalation cohort will initially recruit 3 patients to receive AO-176 in a standard 3+3 design; cohorts will be expanded in the event of a DLT.
    Intervention: Drug: AO-176
  • Experimental: AO-176 Dose Expansion
    Once the MTD/RP2D has been established, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy of AO-176.
    Intervention: Drug: AO-176
  • Experimental: AO-176 + Paclitaxel Dose Escalation
    Each dose escalation cohort will initially recruit 3 patients to receive AO-176 and paclitaxel in a standard 3+3 design; cohorts will be expanded in the event of a DLT.
    Intervention: Drug: AO-176 + Paclitaxel
  • Experimental: AO-176 + Paclitaxel Dose Expansion
    Once the MTD/RP2D has been established, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy of AO-176 + paclitaxel.
    Intervention: Drug: AO-176 + Paclitaxel
  • Experimental: AO-176 + Pembrolizumab Dose Escalation
    Each dose escalation cohort will initially recruit 3 patients to receive AO-176 and pembrolizumab in a standard 3+3 design; cohorts will be expanded in the event of a DLT.
    Intervention: Drug: AO-176 + Pembrolizumab
  • Experimental: AO-176 + Pembrolizumab Dose Expansion
    Once the MTD/RP2D has been established, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy of AO-176 + pembrolizumab.
    Intervention: Drug: AO-176 + Pembrolizumab
Publications * Andrejeva G, Capoccia BJ, Hiebsch RR, Donio MJ, Darwech IM, Puro RJ, Pereira DS. Novel SIRPα Antibodies That Induce Single-Agent Phagocytosis of Tumor Cells while Preserving T Cells. J Immunol. 2021 Feb 15;206(4):712-721. doi: 10.4049/jimmunol.2001019. Epub 2021 Jan 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 3, 2021)
183
Original Estimated Enrollment  ICMJE
 (submitted: February 6, 2019)
90
Estimated Study Completion Date  ICMJE March 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria

  1. Select advanced solid tumor for which standard therapy proven to provide clinical benefit does not exist, or is no longer effective

    Part A:

    • Epithelial ovarian carcinoma (EOC)
    • Endometrial carcinoma
    • Castration resistant prostate cancer
    • Non-small cell lung adenocarcinoma
    • Papillary thyroid carcinoma
    • Malignant mesothelioma (pleural or peritoneal)
    • Gastroesophageal adenocarcinoma
    • Squamous cell carcinoma of the head and neck

    Part B and Part C:

    • Platinum-resistant EOC (including fallopian tube or primary peritoneal cancer)
    • Endometrial carcinoma
    • Gastric adenocarcinoma/gastroesophageal adenocarcinoma
  2. Measurable disease
  3. ECOG status 0-1
  4. Resolution of prior-therapy-related adverse effects
  5. Minimum of 4 weeks or 5 half-lives since last dose of cancer therapy

Key Exclusion Criteria:

  1. Previous hypersensitivity reaction to treatment with another monoclonal antibody
  2. Unresolved hypersensitivity to paclitaxel or any of its excipients (Part B only). Patients who have been desensitized may participate.
  3. Part C Only

    1. History of interstitial lung disease or a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
    2. History of immune mediated colitis, hepatitis, endocrinopathies, nephritis or significant immune mediated skin reactions such as toxic epidermal necrolitis or Stevens -Johnson Syndrome
    3. History of any autoimmune disease which required systemic therapy* in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) including but not limited to: i. Inflammatory bowel disease (including ulcerative colitis and Crohn's Disease) ii. Rheumatoid arthritis iii. Systemic progressive sclerosis (scleroderma) iv. Systemic lupus erythematosus v. Autoimmune vasculitis (e.g. Wegener's granulomatosis) *Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed)
  4. Prior treatment with a checkpoint inhibitor (anti-PD-1, PD-L1, CTLA-4 etc.) within 4 weeks prior to the start of study drug
  5. Prior treatment with a CD47-targeted therapy
  6. Prior organ or stem cell transplant
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Arch Medical Monitor 415-671-4035 AO-176-101-CT.gov@archoncology.com
Contact: Sergio Rodriguez srodriguez@archoncology.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03834948
Other Study ID Numbers  ICMJE AO-176-101
KEYNOTE-C49 ( Other Identifier: Merck Sharp & Dohme Corp. )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Arch Oncology
Study Sponsor  ICMJE Arch Oncology
Collaborators  ICMJE Merck Sharp & Dohme LLC
Investigators  ICMJE
Study Director: Naimish Pandya Arch Oncology
PRS Account Arch Oncology
Verification Date April 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP